Pruritus is an unpleasant itching sensation that triggers the desire to scratch. Vigorous scratching may cause redness and deep scrapes in the skin. If the scratching causes breaks in the skin, an infection may result. Scratching can irritate the skin and lead to more itching, creating an itching-scratching-itching cycle. Prolonged scratching and rubbing can thicken and scar the skin. Pruritus can be related to anything from dry skin to undiagnosed disease. Itching may be caused by a skin disorder or by a systemic disease. The neurotransmitter histamine is known to be involved in itching, and administration of topical histamine can elicit itching. For many subjects, anti-histamines ameliorate itching, at least to some degree, but histamine cannot account for all aspects of pruritus. Current research indicates that pruritus may be induced by histamine-independent mechanisms as well. Subjects with chronic itching that fails to respond to conventional therapies (e.g., anti-histamines, corticosteroids) may experience sleep disturbances or depression. Given that current methods of treating itching are inadequate, improved methods for alleviating pruritus are urgently required.